Throughout the animal kindgdom, territorial and reproductive behaviors are often innate, indicating that their underlying neural substrates are genetically hardwired. Among vertebrates, many of these behaviors are controlled by the steroid hormone testosterone and its metabolites. Exposure of developing and adult brains to testosterone results in the masculinization of behavior, and in males of most species testosterone (or a metabolite) is necessary for the elicitation of mating and aggressive behavior as adults. The production of gonadal steroids such as testosterone is controlled by neurons of the hypothalamus expressing the neuropeptide gonadotropin releasing hormone (GnRH1). Some of these neurons project to the pituitary, where they control the release of the gonadotropins luteinizing hormone and follicle stimulating hormone into the bloodstream. These hormones bind receptors in the testes, stimulating the production of testosterone. Another subset of GnRH1 neurons project elsewhere in the brain, but the functional relevance of these neurons has not been tested. GnRH1 neurons exhibit dynamic cellular, electrophysiological, and gene transcription correlates of reproductive and territorial behaviors, making them candidate neurons to regulate behavioral outputs. To manipulate GnRH1 neurons, I will transgenically modify a cichlid fish, Astatotilapia burtoni, to express nitroreductase specifically in these cells, enabling their ablation in a temporally controlled manner. Experiments utilizing these fish in this proposal will directly test the function of GnRH1 neurons for behavior in transgenic adult A. burtoni. Further, comparison of the behavioral effects of hormone manipulation to GnRH1 neuron ablation will reveal the relative contributions of GnRH1 neurons to reproductive and territorial behavior via hormone synthesis versus direct connections to the neural circuits that generate these behaviors. This transgenic animal model in which GnRH1 neurons can be conditionally ablated in adult fish will provide a system to understand how these neurons contribute to behavior, and may provide insight into their regulation of fertility, puberty, and menopause.

Public Health Relevance

In all vertebrates, gonadotropin releasing hormone (GnRH1) controls levels of gonadal hormones such as testosterone and estrogen. The proposed experiments will identify how GnRH1 regulates reproductive and aggressive behaviors. Results of these experiments will provide basic insights into how the brain generates behavior, and will provide a model system for endocrine-related disorders such as infertility, delayed puberty, and premature menopause.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD071755-03
Application #
8616086
Study Section
Special Emphasis Panel (ZRG1-F02A-J (20))
Program Officer
Lamar, Charisee A
Project Start
2012-03-07
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
3
Fiscal Year
2014
Total Cost
$55,094
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Juntti, Scott A; Hu, Caroline K; Fernald, Russell D (2013) Tol2-mediated generation of a transgenic haplochromine cichlid, Astatotilapia burtoni. PLoS One 8:e77647